Flightless I homolog negatively regulates ChREBP activity in cancer cells

Wu, Lifang; Chen, Hanbei; Zhu, Yemin; Meng, Jian; Li, Yakui; Li, Minle; Yang, Dianqiang; Zhang, Ping; Feng, Ming; Tong, Xuemei

doi:10.1016/j.biocel.2013.09.004

Cited by 20 publications

(30 citation statements)

References 36 publications

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“…PI3K and small GTPases may regulate the subcellular localization of FLII between cytoplasm and nucleus (15). FLII has been found to interact with various proteins important for cellular signaling (15). FLII may function as a transcriptional coregulator which positively or negatively regulates the activity of transcription factors (15).…”

Section: Introductionmentioning

confidence: 99%

“…FLII has been found to interact with various proteins important for cellular signaling (15). FLII may function as a transcriptional coregulator which positively or negatively regulates the activity of transcription factors (15). FLII can be recruited by hormone-activated nuclear receptors to the promoters of target genes to serve as a coactivator of the nuclear receptor transcription complex (14,16,17).…”

Section: Introductionmentioning

confidence: 99%

“…FLII can be recruited by hormone-activated nuclear receptors to the promoters of target genes to serve as a coactivator of the nuclear receptor transcription complex (14,16,17). FLII also negatively regulates PPARg, b-catenin, and ChREBP-mediated transcription in cancer cells (15,18,19). It is currently unknown whether FLII plays a role in AR function during prostate cancer development.…”

Section: Introductionmentioning

confidence: 99%

“…LRR of FLII is implicated in protein-protein interaction and many have identified that these binding partners and GLD of FLII have some unique regulatory function (13). PI3K and small GTPases may regulate the subcellular localization of FLII between cytoplasm and nucleus (15). FLII has been found to interact with various proteins important for cellular signaling (15).…”

Section: Introductionmentioning

confidence: 99%

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Flightless I Homolog Represses Prostate Cancer Progression through Targeting Androgen Receptor Signaling

Wang

Song

Chen

et al. 2016

Clinical Cancer Research

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Purpose: Flightless I (FLII), member of the gelsolin superfamily of actin-remodeling proteins, functions as a transcriptional coregulator. We aim to evaluate a tumor-suppressive function of FLII in regulating androgen receptor (AR) in prostate cancer progression.Experimental Design: We examined FLII protein and mRNA expression in clinical prostate cancer specimens by immunohistochemistry. Kaplan-Meier analysis was conducted to evaluate the difference in disease-overall survival associated with the expression levels of FLII and AR. Prostate cancer cells stably expressing FLII or shRNA knockdown were used for functional analyses. Immunoprecipitation, Luciferase reporter, and immunofluorescence staining assays were performed to examine the functional interaction between FLII and AR.Results: Our analysis of the expression levels of FLII in a clinical gene expression array dataset showed that the expression of FLII was positively correlated with the overall survival of prostate cancer patients exhibiting high levels of AR expression. Examination of protein and mRNA levels of FLII showed a significant decrease of FLII expression in human prostate cancers. AR and FLII formed a complex in a ligand-dependent manner through the ligand-binding domain (LBD) of AR. Subsequently, we observed a competitive binding to AR between FLII and the ligand. FLII inhibited AR transactivation and decreased AR nuclear localization. Furthermore, FLII contributed to castration-sensitive and castration-resistant prostate cancer cell growth through AR-dependent signaling, and reintroduction of FLII in prostate cancer cells sensitized the cells to bicalutamide and enzalutamide treatment.Conclusions: FLII plays a tumor-suppressive role and serves as a crucial determinant of resistance of prostate cancer to endocrine therapies.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Flightless I Homolog Represses Prostate Cancer Progression through Targeting Androgen Receptor Signaling

Wang

Song

Chen

et al. 2016

Clinical Cancer Research

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show abstract

“…ChREBP is a basic helix-loop-helix/leucine zipper transcription factor that is expressed in several metabolically relevant tissues, including liver, adipocytes, pancreatic b-cells, and certain cancer cells, and is a mediator of glucose-responsive gene activation [21][22][23]. Upon activation by glucose, ChREBP translocates from the cytosol into the nucleus, thereby forming a heterodimer with Max-like protein X (Mlx) that binds to the carbohydrate response element (ChRE) for transcriptional regulation of genes associated with glucose, lipid, fatty acid, and steroid metabolism [24].…”

mentioning

confidence: 99%